Activatable\nPhotodynamic Therapy with Therapeutic\nEffect Prediction Based on a Self-correction Upconversion Nanoprobe

Abstract

Though\nemerging as a promising therapeutic approach for cancers,\nthe crucial challenge for photodynamic therapy (PDT) is activatable\nphototoxicity for selective cancer cell destruction with low “off-target”\ndamage and simultaneous therapeutic effect prediction. Here, we design\nan upconversion nanoprobe for intracellular cathepsin B (CaB)-responsive\nPDT with <i>in situ</i> self-corrected therapeutic effect\nprediction. The upconversion nanoprobe is composed of multishelled\nupconversion nanoparticles (UCNPs) NaYF₄:Gd@NaYF₄:Er,Yb@NaYF₄:Nd,Yb, which covalently modified with an\nantenna molecule 800CW for UCNPs luminance enhancement under NIR irradiation,\nphotosensitizer Rose Bengal (RB) for PDT, Cy3 for therapeutic effect\nprediction, and CaB substrate peptide labeled with a QSY7 quencher.\nThe energy of UCNPs emission at 540 nm is transferred to Cy3/RB and\neventually quenched by QSY7 via two continuous luminance resonance\nenergy transfer processes from interior UCNPs to its surface-extended\nQSY7. The intracellular CaB specifically cleaves peptide to release\nQSY7, which correspondingly activates RB with reactive oxygen species\n(ROS) generation for PDT and recovers Cy3 luminance for CaB imaging.\nUCNPs emission at 540 nm remains unchanged during the peptide cleavage\nprocess, which is served as an internal standard for Cy3 luminance\ncorrection, and the fluorescence intensity ratio of Cy3 over UCNPs\n(FI583/FI540) is measured for self-corrected therapeutic effect prediction.\nThe proposed self-corrected upconversion nanoprobe implies significant\npotential in precise tumor therapy.